Several polypeptides with the potential to cause blood vessel growth (angiogenesis) have been sequenced and synthesized during the last few years. Our ultimate goal is to utilize these angiogenic agent(s) to facilitate myocardial revascularization in patients with coronary heart disease. Basic fibroblast growth factor (bFGF) is a potent angiogenic peptide that may play an important role in coronary collateral formation. We previously found that intracoronary administration of bFGF increases collateral blood flow (CBF) in vivo, in a canine model of myocardial ischemia. In this study, we examined the effect of systemic bFGF on CBF in the same model, and assessed its potential side effects. Progressive constriction of the LCX coronary artery was induced of 20 dogs by placing ameroid constrictors on the vessel. Beginning on day 10, dogs received daily injection of bFGF (1.74 mg, n=10) or saline (n=10) into the left atrium. Treatment was maintained for 28 days. Microsphere blood flow was determined during maximal vasodilation on a weekly basis, beginning on day 3. CBF was expressed as an ischemic/normal zone (IZ/NZ) ratio. No adverse systemic effects were apparent. During the first week of treatment, the IZ/NZ ratio improved from 0.06 to 0.34 in bFGF treated dogs, while improving from 0.12 to 0.16 in controls (p=0.015, bFGF vs. control). During the second week, the IZ/NZ ratio increased from 0.34 to 0.42 in bFGF treated dogs, and from 0.16 to 0.19 in controls (p<0.001, bFGF vs. control). The disparity between groups, however, diminished during the third and fourth weeks of treatment. The acceleration of collateral formation was similar to that observed previously with intracoronary administration. The "catch up" phenomenon observed during weeks 3 and 4 suggests that there is a ceiling for the bFGF response, or, more likely, the observed increase in CBF abolishes ischemia in this canine model of single vessel coronary occlusion, thereby removing any further stimulus to collateral development.